Precision Treatment Would Benefit Patients With Glioblastoma, Stanford Analysis Finds

When researchers at Stanford University dug deep into data from 2 “failed” glioblastoma trials, they found that a subgroup of patients in each of the trials did respond to the angiogenesis inhibitor bevacizumab—however, non-responders washed out the effect observed in the cohort that had highly vascularized tumors.

The results from both trials were published in the New England Journal of Medicine^1,2 in 2014.

The first trial, called Radiation Therapy Oncology Group (RTOG) 0825, randomized 637 adults to receive bevacizumab or placebo during week 4 of treatment with radiotherapy and temozolomide, which was continued for up to 12 cycles of maintenance chemotherapy. Trial end points were 25% reduction in risk of death and a 30% reduction in the risk of progression or death, following bevacizumab treatment. The trial found no significant difference in the median overall survival (OS) in the 2 patient cohorts—those receiving placebo (16.1 months) versus bevacizumab (15.7 months).

The second trial, Avastin in Glioblastoma (AVAglio) study, randomized 921 patients with supratentorial glioblastoma to receive either bevacizumab or placebo, in combination with radiotherapy and temozolomide. After a 28-day break, patients received maintenance bevacizumab or placebo, with temozolomide for six 4-week cycles, followed by bevacizumab monotherapy. Progression-free survival (PFS) and OS were the co-primary endpoints.

Both trials reported improved PFS, but not OS.

The new research at Stanford, which is published in Neuro-Oncology,³ was led by Daniel Rubin, MD, associate professor of biomedical sciences, radiology, and medicine, at Stanford University School of Medicine. The authors retrospectively analyzed the medical records and diagnostic images of 69 glioblastoma patients who had been treated at a local medical center and 48 from The Cancer Genome Atlas. Patients were classified into 1 of 2 groups: highly-vascularized tumors or less-vascularized tumors. The authors found that 51 patients in their study group had highly-vascularized tumors, while 66 had tumors that were not well-vascularized. Additionally, the authors noted that genetic analysis of these tumors identified the expression of genes that have known function in blood vessel growth and protection from hypoxia.

Subgroup analysis showed that patients who had a greater degree of angiogenesis survived upto a year longer when treated with antiangiogensis drugs, compared with when they were treated with other forms of chemotherapy.

“Our findings speak to the fact that the biology of glioblastoma can vary significantly among individuals, and that certain subgroups of patients may benefit from treatments that appear ineffective when screened across a large unselected mix of patients,” Rubin said in an associated press release. He added that their results highlight the importance of subtyping cancers to have a significant impact on disease treatment.

References

1. Gilbert MR, Dignam JJ, Armstrong TS, et al. A randomized trial of bevacizumab for newly diagnosed glioblastoma. N Engl J Med. 2014;370(8):699-708. doi: 10.1056/NEJMoa1308573.
2. Chinot OL, Wick W, Mason W, et al. Bevacizumab plus radiotherapy—temozolomide for newly diagnosed glioblastoma. N Engl J Med. 2014;370(8):709-722. doi: 10.1056/NEJMoa1308345.
3. Liu TT, Achrol AS, Mitchell LA, et al. Magnetic resonance perfusion image features uncover an angiogenic subgroup of glioblastoma patients with poor survival and better response to antiangiogenic treatment [published online December 22, 2016]. Neuro Oncol. doi: 10.1093/neuonc/now270.